The use of enzymes in organic syntheses has become prevalent. By exploiting the tools that nature provides, chiral molecules can be selectively separated or resolved, or chirality can be infused into a molecule having no chirality, by virtue of the enzyme's own chiral nature. Enzymes provide precise stereocontrol and accelerate chemical transformations that are otherwise difficult to carry out using conventional synthetic chemistry. More importantly, enzymes generally obviate the need for protecting group manipulations frequently hampering and adding additional steps in a chemical synthesis. As such, enzymes are commercially used to synthesize and/or resolve active pharmaceuticals and useful intermediates leading thereto.
Many carbon based pharmaceuticals as well as intermediates have chiral centers which permit multiple stereoisomers or antipodes. Typically, each stereoisomer has distinct chemical and physical properties. Some of those properties can be fatal and some can be pharmaceutically useful. For example, (S)-thalidomide can cause severe birth defects, while (R)-thalidomide is a safe and effective sedative, and a treatment for diseases such as cancer. These dramatic differences have led the Food and Drug Administration to require each enantiomer of a racemic drug to be put through clinical testing individually prior to receiving approval for widespread distribution. Thus, there is a need for stereoselective methods for synthesizing or enriching stereoisomers. In particular, there exists a need for biocatalytic process for synthesizing enantiomeric or diastereomerically pure pharmaceutical and intermediates.